Schnitzler syndrome: validation and applicability of diagnostic criteria in real-life patients.

BACKGROUND: Schnitzler syndrome is characterized by an urticarial rash, a monoclonal gammopathy, and clinical, histological, and biological signs of neutrophil-mediated inflammation. The aim of this study was to assess the applicability and validity of the existing diagnostic criteria in real-life patients. METHODS: This multicentric study was conducted between 2009 and 2014 in 14 hospitals in which patients with Schnitzler syndrome or controls with related disorders were followed up. We compared the sensitivities and specificities and calculated the positive and negative predictive values of the Lipsker and of the Strasbourg criteria for the patients with Schnitzler syndrome and for the controls. We included 42 patients with Schnitzler syndrome, 12 with adult-onset Still's disease, 7 with cryopyrin-associated periodic disease, 9 with Waldenström disease, and 10 with chronic spontaneous urticaria. RESULTS: All patients with Schnitzler syndrome met the Lipsker criteria. According to the Strasbourg criteria, 34 patients had definite Schnitzler syndrome, five had probable Schnitzler syndrome, and three did not meet the criteria. One control met the Lipsker criteria and had probable Schnitzler syndrome according to the Strasbourg criteria. Sensitivity and specificity of the Lipsker criteria were 100% and 97%, respectively. For the Strasbourg criteria, sensitivity for definite and probable diagnosis was 81% and 93%, respectively, with a corresponding specificity of 100% and 97%. CONCLUSION: Diagnostic criteria currently in use to diagnose Schnitzler syndrome are reliable. More investigations must be done to attest their efficiency in patients with recent-onset manifestations.

Multidimensional analysis of clinical symptoms in patients with Fabry's disease.

AIM: Fabry's disease is an X-linked inherited lysosomal storage disorder caused by the deficient activity of alpha-galactosidase A. The interrelationships between clinical symptoms in Fabry patients have not yet been fully established. Using cluster and multivariate analysis, the aim of the study was to determine the relationships among clinical symptoms and organ involvement, and predictive clinical symptoms for disease severity. METHODS: Clinical data obtained from 108 French Fabry patients were retrospectively collected and analysed using multiple correspondence analysis and hierachical ascendant classification. Multivariate analysis was also performed to determine among clinical symptoms predictors for cardiac disease (HRT), renal involvement (KDN) and brain complication (STR). RESULTS: The cohort comprised 41 male patients (aged 28.9 ± 11.6 years) and 67 female patients (aged 40.4 ± 15.5 years). Three main clusters of clinical symptoms could be delineated, characterising disease progression: the first cluster grouped digestive disorders (found in 30% of the patients) and exercise intolerance (32%), the second, cluster dyshidrosis (47%), acroparesthesia (67%), angiokeratoma (44%) and cornea verticillata (54%), the third, cluster grouped KDN (30%), HRT (39%) and STR (25%) and hearing loss (44%). In univariate analysis, the patient age predicted HRT and KDN, dyshidrosis predicted HRT and STR, angiokeratoma predicted KDN and cornea verticilla and hearing loss predicted KDN, HRT and STR. In multivariate analysis, hearing loss and age were independent predictors of organ complication. CONCLUSION: Among the various interrelated clinical symptoms occurring in Fabry disease, patients with dyshidrosis and particularly hearing disorders appear to be at higher risk of organ complications.

Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

[Systemic Rosai-Dorfman-Destombes disease associated with a myelodysplastic syndrome. Efficacy of hematologic treatment]. / Maladie de Rosai-Dorfman-Destombes (RDD) multifocale réfractaire associée à un syndrome myélodysplasique. Efficacité du traitement hématologique.

INTRODUCTION: We report an original observation of multifocal refractory Destombes-Rosai-Dorfman disease associated with a myelodysplastic syndrome. The treatment of myelodysplasia allowed a good and prolonged response of both pathologies. CASE REPORT: A 35-year-old patient was investigated for bilateral exophthalmia, histologically related to Destombes-Rosai-Dorfman disease. The extension workup showed sinus, kidney and lymph node involvement. It was treated unsuccessfully with corticosteroids, colchicine, methotrexate, infliximab, cladribine and tociluzimab. The secondary appearance of myelodysplasia (AREB IPSS score intermediate-2) led to induction treatment with aracytin and idarubicin, and maintenance with azacytidine for 2 years. With 5 years of follow-up, the patient is in remission both of the myelodysplastic syndrome and Destombes-Rosai-Dorfman disease. CONCLUSION: Our observation discusses the interest of the treatment of myelodysplastic syndrome for the management of associated extra-hematological manifestations.

[Xanthelasma associated with Wegener's granulomatosis]. / Xanthélasmas et granulomatose de Wegener.

BACKGROUND: There have been rare reports of normolipidaemic xanthelasma in Wegener's granulomatosis. Herein, we describe another case associated with a review of the literature. CASE REPORT: A 62-year-old woman was hospitalized for Wegener's disease with cutaneous, ENT, renal, joint and neurological signs. Physical examination showed bilateral palpebral xanthelasma with infiltrated lacrimal glands that had appeared simultaneously to the other clinical signs. No hyperlipidaemia was noted. Biopsy of the xanthelasma revealed a typical infiltrate of foamy histiocytes and focal vasculitis. On treatment with corticoids and cyclophosphamide, the yellow lid lesions gradually disappeared. DISCUSSION: Normolipidaemic xanthelasma is rarely reported in association with Wegener's granulomatosis. It accompanies local ophthalmological inflammation and its appearance during the course of this disease must be dealt with carefully.

[Sarcoidosis-like granulomatosis revealing a tertiary syphilis]. / Granulomatose pseudosarcoïdosique révélant une syphilis tertiaire.

Numerous disorders can cause a systemic granulomatosis. We report a patient who presented a biopsy proven granulomatous skin eruption, fever, and atypical thoracic pain. Electrocardiogram showed a first-degree atrioventricular heart bloc. During follow-up he developed a panuveitis and oral corticosteroids were started. A diagnosis of systemic sarcoidosis was considered. Because of unfavourable ophthalmologic outcome, investigations were enlarged and revealed a highly positive serology for syphilis and VDRL both in serum and cerebrospinal fluid. Clinical outcome with penicillin G therapy was favorable. This observation reminds us the clinical polymorphism of syphilis, which can be presented as a systemic granulomatosis.

[Diagnostic journey of type 1 Gaucher Disease patients: A survey including internists and hematologists]. / Parcours diagnostique des patients atteints de maladie de Gaucher de type 1 : enquête auprès de médecins internistes et hématologues.

INTRODUCTION: Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist. METHODS: A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011. RESULTS: Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician. CONCLUSION: GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.

[Non tuberculous mycobacterial infections]. / Les infections à mycobactéries non tuberculeuses.

PURPOSE: Non tuberculous mycobacterial (NTM) infections, also called atypical mycobacterial infections, are caused by environmental mycobacteria and usually occur in cases of general or local immunosupression. These infections usually concern the lungs, the lymphatic system, the skin or the bones tissues. They are sometimes disseminated. In spite of new efficient antibiotics, including macrolides, therapeutic failures are common and favoured by long treatments with their potential adverse effects and drug interactions. CURRENT KNOWLEDGE AND KEY POINTS: The prevalence of atypical mycobacterial infections is increasing and is also observed in internal medicine and geriatric wards. Their clinical expression can be varied. Nowadays, these infections are more and more frequent in non-infected HIV patients, whether immunosupressed or not. Concerning other localisations of atypical mycobacterial infections, iatrogenic causes seem to be increasing and cases of nosocomial transmissions have also been described. When a NTM is found in a sample, its role in the cause of an infection must be assessed with criterias distinguishing infection from colonisation. FUTURE PROSPECTS AND PROJECTS: For those who are not locally or generally immunosupressed, it is important to search for an immunological deficiency. Indeed, patients having congenital deficiencies occurring in the interferon and interleukine pathways can develop repeated NTM infections. Therefore, for pulmonary infections in treatment failure and for disseminated infections, an adjuvant treatment by interferon gamma could be proposed. New molecules have recently been tested and can be used in some atypical mycobacterial infections.

[Chronic histiocytic intervillositis: Diagnosis and management]. / Intervillites chroniques histiocytaires : bilan et prise en charge.

Chronic intervillositis is a rare condition, which is associated with severe obstetrical outcome and high recurrence rate. Obstetrical adverse events are intrauterine growth restriction, recurrent early miscarriages, intrauterine deaths and prematurity by placental insufficiency. The determination of the extension and the intensity of the chronic intervillositis are not currently standardized. High rates of recurrence have been described, but actually there is no reliable predictive biomarker. No treatment is currently validated, but the use of immunomodulatory drugs could be justified by the possible autoimmune or allo-immune origin. The treatment should be particularly discussed in patients with recurrent and severe obstetrical adverse events and in the presence of severe and massive histological lesions.

Churg-Strauss syndrome revealed by granulomatous acute pericarditis: two case reports and a review of the literature.

BACKGROUND: Churg-Strauss syndrome (CSS) is a necrotizing systemic vasculitis with extravascular granulomas and eosinophilic infiltrates of small vessels. CSS is usually revealed by nonspecific signs of necrotizing vasculitis in a context of late-onset asthma and blood eosinophilia. It is considered a systemic vasculitis with the highest prevalence of cardiac involvement and can lead to rapid-onset heart failure due to specific cardiomyopathy. Pericardial effusion may also occur during CSS and is usually well tolerated. OBJECTIVE: The objective of these case reports was to indicate that CSS may present as tamponade, with or without other visceral involvement. METHODS: Among CSS patients treated during the past 10 years at 2 French university hospitals, we have identified and described 2 cases revealed by tamponade with pericardial biopsy-proven granulomatous vasculitis. We have also reviewed the international medical literature in PubMed on cardiac involvement in CSS. RESULTS: The first case report describes a 66-year-old man who had an isolated cardiac tamponade with both inflammatory syndrome and eosinophilia. Long-term remission was obtained with corticosteroids. The second case report describes a 46-year-old woman whose CSS presented with tamponade and associated central nervous system and myocardial involvement. Remission was obtained with corticosteroids and cyclophosphamide. In both cases, CSS was assessed by histological analysis of a pericardial sample. CONCLUSIONS: CSS may present as isolated cardiac tamponade. Whereas pericarditis with myocardial injury warrants immunosuppressive therapy, isolated pericarditis without other visceral involvement of poor prognosis only requires corticosteroid therapy.

[Post-transfusion acute lung injury (Trali) after plasma infusion in a patient having a constitutional thrombotic microangiopathy]. / Syndrome d'oedème pulmonaire lésionnel aigu post-transfusionnel (Trali) après perfusion de plasma frais congelé au cours d'une microangiopathie thrombotique congénitale.

INTRODUCTION: Transfusion-related acute lung injury is a post-transfusion interstitial lung injury. CASE REPORT: We reported a post-transfusion acute lung injury in a 23-years old woman having a chronic thrombotic microangiopathy related to an ADAMTS 13 constitutional deficiency receiving monthly plasma infusion for six years. The temporal relationship between the lung injury and the infusion of fresh frozen plasma led to the diagnosis of transfusion-related acute lung injury. The finding in the donor of the transfused plasma of an anti-HLA class II antibody recognizing HLA-DR52 present on leucocytes of the recipient suggests a causal relationship between this antigen-antibody conflict and the triggering of the TRALI. This chronic pathologic state requiring monthly plasma transfusions for thrombotic accident prevention raises the question of the selection of plasma obtained from non-immunized donors. CONCLUSION: The occurrence of a post transfusion pulmonary edema without cardio-vascular overload, must lead to consider a TRALI especially in predisposing clinical situations. In the case reported the role of constitutional ADAMTS 13 deficiency in genesis of TRALI is considered.

[Transfusion-related acute lung injury]. / Oedème pulmonaire lésionnel aigu post-transfusionnel ou Trali.

OBJECTIVES: The transfusion-related acute lung injury frequency was for a long time underestimated since it lacked both a widely accepted clinical definition and a comprehensive etiologic description. Recent clinical and biological data have underlined its frequency and have allowed a better understanding of its mechanisms. CURRENT KNOWLEDGE AND KEY POINTS: Trali is an interstitial lung injury occurring within 6 hours after the beginning of a blood transfusion. This time relationship between blood injection and the occurrence of lung edema is sufficient for a positive diagnosis, if any other cause of interstitial lung edema have been excluded. The clinical definition relies on a desaturation of arterial blood associated to a lack of any cardiac failure or circulation overload. The link between transfusion and lung edema is not univocal and several categories of mechanisms have been discussed. At least 2 of them are well identified; the first one is an immune conflict, and the second one is an activation of neutrophils by injection of biological modifiers such as lipids or CD40 soluble ligand. Evidences exist for the occurrence of Trali only in predisposing condition that mostly consists of a preceding leucostase in lung capillaries. Trali is treated like other lung interstitial edema by oxygen therapy and mechanical ventilation. FUTURE PROJECTS: A better knowledge of Trali offers the opportunity of improving the understanding of the role of blood transfusion in lung edema occurring in complex situations and open the way for a better definition of at risk patient and at risk blood components.

[Screening of abdominal aortic involvement using Doppler sonography in active giant cell (temporal) arteritis at the time of diagnosis. A prospective study of 30 patients]. / Dépistage de l'atteinte aortique abdominale par échographie-doppler au diagnostic de maladie de Horton. Etude prospective de 30 patients.

BACKGROUND: Inflammatory involvement of extracranial large-sized arteries occurs in 10-20% of patients with giant cell (temporal) arteritis. Aortic involvement may reveal giant cell arteritis or occur as a late-onset complication, and represents one of the most serious manifestation of the disease with the risk of aortic dissection and/or aneurysm rupture. The thoracic aorta is more frequently involved but abdominal aortitis may also occur in giant cell arteritis. To date, few data are available about abdominal aorta changes at the initial stage of giant cell arteritis. PATIENTS AND METHODS: This prospective monocentric study was conducted between May 1998 and May 2002, and included 30 consecutive patients with biopsy-proven giant cell arteritis. Standard clinical and biological data were collected. Each patient underwent an abdominal aortic Doppler-sonography that looked for aneurysm, ectasia, thickening of the vascular wall, and hypoechoic halo around the aorta. RESULTS: Among the 30 patients of this study (25 women, 5 men, mean age 68.5 years), 4 (13%) had an abdominal aortic aneurysm, with a low diameter (23 to 27 mm), measuring 2 to 5.5 cm in length. A vascular wall thickening superior or equal to 3 mm was noted in 17 patients (68%). A 4 to 8 mm periaortic hypoechoic halo was found in 10 patients (33%). This halo was present in 3 out of the 4 patients with aneurysm. CONCLUSION: Aortic involvement is a potentially serious complication of giant cell arteritis. The question of a systematic screening of this complication remains open to discussion. Our study shows that Doppler sonography may detect morphological abnormalities on the abdominal aorta at the initial stage of giant cell arteritis. These abnormalities comprise mild aneurysms, thickening of the vascular wall and periaortic halo, which could correspond to inflammatory locations of the disease. Complementary studies are needed to assess their specificity and their seriousness.

[Endobronchial stenosis in Wegener's granulomatosis]. / Sténoses endobronchiques au cours de la granulomatose de Wegener.

INTRODUCTION: Endobronchial stenoses are rare in the course of Wegener's granulomatosis, and they occur even more rarely than subglottic stenoses. EXEGESIS: We report seven cases of endobronchial stenoses in the setting of Wegener granulomatosis. Neither the pulmonary symptoms nor the systemic manifestations of vasculitis were specific. However 6/7 patients presented a wheezing or an hemoptysis. Bronchial endoscopy has permitted the diagnosis in all cases. Local evolution was cicatricial and symptomatic stenosis in 3 cases (42,8%). CONCLUSION: Thus these lesions must be research in any case of pulmonary abnormality in the course of Wegener's granulomatosis, because they may lead to a pejorative prognosis. Moreover general and local treatment must be given early (at the inflammatory stage). After this stage, the local treatments are difficult and not efficient.

[Qualitative and quantitative evaluation of an internal medicine assistance line dedicated to the diagnosis and treatment of diseases for general practice]. / Évaluation qualitative et quantitative d'un service d'assistance téléphonique de médecine interne dédié à l'aide diagnostique et thérapeutique de pathologies relevant du champ de la médecine générale.

PURPOSE: Clinical reasoning and treatment challenges within the scope of general practice led to the development of an internal medicine assistance line provided by Nantes University Hospital. The primary outcome of this study was to describe callers' profile, their requests and answers provided. METHODS: A prospective, cross-sectional, observational, descriptive study was undertaken. For each call were identified the calling physician, her/his specialty and work setting, the call's object and adequacy, the answer provided, the time needed to connect with the assistance line, the time devoted by the internal medicine physician to provide an answer to the request, and whether the assistance line prevented a visit to the emergency room. Each calling physician was then called back to obtain demographic and professional characteristics, and data relating to the call and to the assistance line. RESULTS: Sixty-three days were analyzed and 276 calls identified. The 237 identified calling physicians were mainly females (54%, n=93), with a mean age of 46 years, graduated from Nantes University (65%, n=86), practicing ambulatory general medicine (69%, n=164) in Loire-Atlantique department area (82%, n=176) for a mean duration of 15 years. Calls were mostly associated with diagnostic challenges (61%, n=166) concerning clinical issues (57%, n=155). A sole telephone advice was the main type of answer provided (56%, n=147) and a visit to the emergency room was prevented for 17% of calls. CONCLUSION: The assistance line activity is adequate with its missions and seems to facilitate patients' healthcare delivery advocating for the development of similar structures in other units. Improvements relating to the information, availability and physicians' training should be considered.

Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients.

OBJECTIVES: The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis. METHODS: Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared. RESULTS: Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA ≥ 60 years when compared to patients with GCA-related aortitis. CONCLUSIONS: IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA ≥ 60 years share many features with GCA-related aortitis.

[Strongyloides stercoralis infection simulating polyarteritis nodosa]. / Anguillulose autochtone simulant une périartérite noueuse.

INTRODUCTION: Parasitic infection can present with many different clinical manifestations. EXEGESIS: A 77 year-old Russian woman, who's been living in France since 50 years was admitted for polyarthritis, myalgia, fever, abdominal pain, and eosinophilia simulating polyarterisis nodosa. Before admission, she was treated by steroids for polymyalgia rheumatica. The diagnosis of Strongyloides stercoralis was performed by parasitologic analysis of feces and colic biopsies. The outcome was favourable under treatment by ivermectine and steroid withdrawal. CONCLUSION: S. stercoralis can be associated with reactive arthritis. Case reports of S. stercoralis infection mimicking systemic vasculitis are exceptionnal.

[Plasma exchanges as treatment of severe acute immune thrombocytopenic purpura]. / Echanges plasmatiques dans les formes graves de purpura thrombopénique immunologique aigu.

INTRODUCTION: High dose steroids and intravenous immunoglobulins are the gold treatment of acute immune thrombocytopenic purpura, before splenectomy for severe and refractory forms of the disease. Authors report two cases of severe acute refractory immune thombocytopenia with a dramatic response to plasma exchanges. EXEGESIS: The first case was an idiopathic form, complicated by hemorragic peritoneal effusion. After failure of steroids, intravenous immunoglobulins and splenectomy and 2 courses of rituximab, plasmapheresis normalized in 3 days platelet count. In the second observation, ITP was associated to systemic lupus with antiphospholipids antibodies and multivisceral failure, despite steroids and intravenous immunoglobulins. After 3 plasma exchanges, platelet count was normalized, and the patient is under remission after 24 months follow-up. CONCLUSION: Plasmapheresis must be evaluated as an emergency treatment in refractory forms of acute immune thrombocytopenic purpura.

[Adult-onset Still disease with hemophagocytic syndrome treated with cyclosporine]. / Maladie de Still de l'adulte avec syndrome d'activation macrophagique. Intérêt de la ciclosporine.

INTRODUCTION: Adult-onset Still disease can have severe manifestations, the treatment of which is not yet codified. CASE: The authors report a case of life-threatening adult-onset Still disease with hemophagocytic syndrome, which improved dramatically with cyclosporin A. Despite the presence of severe pancytopenia, adult-onset Still disease is suggested by the combination of sore throat, myalgia, rash, hepatitis, high serum ferritin, low glycosylated ferritin, and negative etiologic findings. DISCUSSION: Still disease may be present in patients with febrile pancytopenia, and cyclosporine may be a useful treatment after corticosteroid failure.